1) Field of the Invention
The present invention relates to a process for efficiently producing an alcohol or an amine.
2) Description of the Background Art
Conventional approaches for reducing organic functional groups include reduction using a metal hydride such as lithium aluminum hydride or sodium borohydride and hydrogenation using a transition metal catalyst such as platinum oxide, ruthenium carried by activated carbon or Cu-Cr catalyst.
However, these approaches have at least one of the following problems.
(1) A severe reaction condition such as high temperature/high pressure is required.
(2) Only limited functional groups can be reduced.
(3) If applied to a functional group having a great steric hindrance, the yield of the product is low.
(4) The reducing agent is sometimes not readily available because it is not industrially produced. Moreover, even when industrially produced, it is instable to the moisture contained in the atmosphere or in the reaction system and therefore is not free from the danger of ignition.
For example, when organic functional groups are reduced without using any transition metal catalyst, the use of lithium aluminum hydride is accompanied by the danger of ignition because it is very instable to the moisture contained in the reaction system or in the atmosphere. In this respect, sodium borohydride is suitable for the industrial use because it is stable against the moisture contained in the reaction system or in the atmosphere. This approach of using sodium borohydride alone, however, has only limited applications: Aldehydes, ketones and acid chlorodies are successfully reduced; oxiranes, esters and lactones are reduced at a very slow reaction speed; carboxylates, tertiary amides and nitriles cannot be reduced.
Further, in order to improve the reducing ability of sodium borohydride, several approaches have been proposed, which include a method of effectively reducing esters, lactones or oxiranes by having a sodium borohydride and a lithium halogenide coexist and converting the sodium borohydride into lithium borohydride in the system (Tetrahedron vol. 35, p567-607 (1979)) and a method of reducing acid amides, nitriles or carboxylic acids by making a carboxylic acid react on a sodium borohydride and converting it into an acylated sodium borohydride (Journal of Organic Synthetic Chemistry Association, 35(4), 300-303, 1977). It has also been reported that tertiary and primary amides can be reduced by using pyridine as a solvent. Recently, it has been reported that a method of using tetrahydrofuran, diglyme (diethylene glycol dimethyl ether), t-butanol or the like as a solvent and adding methanol dropwise to the system can successfully reduce esters, lactones, oxiranes and disulfides in the presence of sodium borohydride (Bull. Chem. Soc. Jpn., 57, 1948-1953 (1984)), and nitriles, nitro compounds, primary amides and carboxylic acids can be reduced in the presence of lithium borohydride (J. Chem. Soc., Chem. Commun., 668 (1983), J. Org. Chem., 51, 4000 (1986)).
However, lithium borohydride is not industrially supplied, and for obtaining it from sodium borohydride and a lithium halogenide, a large amount of expensive lithium salt is required. Moreover, an acylated sodium borohydride may be deactivated when certain solvents are used. Any one of the above methods of reducing amides requires a large amount of sodium borohydride, and at least five times the molar amount of the substrate. Besides, tertiary amides and nitriles can be reduced only in low yields and esters cannot be reduced at all. On the other hand, when sodium borohydride itself is used, nitriles, nitro compounds, amides and carboxylic acids cannot be reduced even by the method of using tetrahydrofuran, diglyme, t-butanol or the like as a solvent and adding methanol dropwise to the reaction system. Moreover, a large amount of solvent and methanol is required for the reduction of esters, lactones and oxiranes, which means very low industrial productivity. The method of using sodium borohydride and a solvent pyridine has some drawbacks; secondary amides cannot be reduced; tertiary amides can be reduced but yield is low; nitriles are byproduced from primary amides.
Turning to the hydrogenation reaction which proceeds in the presence of a transition metal catalyst, it is an economical process but was found to have the following problem: When applied to compounds having keto groups which have a great steric hindrance, the reaction stops at an equilibrium state where a large residual amount of ketone is left and the conversion cannot proceed even under conditions of high temperature, high hydrogen pressure, and a use of any one of platinum oxide, ruthenium carried by activated carbon or Cu-Cr catalyst. That is to say, for a compound having a functional group of a great steric hindrance, this method could not lead to a satisfactory yield.
For example, the present inventors disclosed a method of producing bornane-3-spiro-1'-cyclopentane-2-ol (III), which is a very useful compound as an odorant substance, by reducing bornane-3-spiro-1'-cyclopentane-2-one (II) with hydrogen by the use of ruthenium carried by activated carbon as a catalyst (Japanese Patent Application Kokai No. 121,938/1990). However, when the ketone (II) was reduced under the condition of high temperature and high hydrogen pressure by the use of this catalyst, the reaction stopped at an equilibrim state where a large amount of the ketone (II) was left and the conversion rate could not be successfully enhanced.
If a lithium aluminum hydride is used, bornane-3-spiro-1'-cyclopentane-2-one can be quantitatively reduced. However, to carry out this reduction on an industrial scale, a special care is needed in handling this reagent because it is very sensitive to the moisture, and the solvent must be strictly purified. Thus, this method is not a simple and economical one. In contrast, use of alkali metal borohydride, whose handling is not so restricted compared to lithium aluminum hydride, is accompanied by a drawback in that when applied to bornane-3-spiro-1'-cyclopentane-2-one (II), and when a lower alcohol, diethyl ether or tetrahydrofuran is used as a solvent, the yield is very low or the reaction does not proceed at all. It is inferred that this ketone compound (II) is difficult to be reduced because of the steric hindrance of the carbonyl group. Recently, in order to improve the reducting ability, a modified process has been developed, where a solvent mixture system of an ether solvent such as tetrahydrofuran-methanol or the like and a lower alcohol is utilized (Bull, Chem. Soc. Jpn., 57, 1948-1953 (1984)). However, sodium borohydride in an amount at least 2.5 times the amount of the substrate and a large amount of a solvent at least 10 times the volume of the substrate are required to complete the reaction by this method. Thus, implementation of this method on an industrial scale is not advisable in terms of the productivity and economy.